The purpose of this proposal is to investigate the mechanisms for the alterations in renal function observed in rats fed a low protein diet by the use of clearance and micropuncture techniques and by the use of tissue slices. Two stages will be studied: 1) when low protein diet has been fed for a short period of time and hypoalbuminemia is not present; and 2) when hypoalbuminemia is a consequence of the low protein diet. Moreover, we wish to determine if the age of the animal influences the effect of the low protein diet on renal function. We wish to test the hypothesis that, although undetected experimentally by the measurement of plasma and extracellular fluid volume, early extracellular fluid loss triggers the intrarenal synthesis of angiotensin II which, by altering intrarenal hemodynamics, perpetrate a state of low filtration rate and hormonal inbalance. We suggest that an increase in renal renin secretion and/or in the intrarenal binding of angiotensin II, together with plasma aldosterone will be indicators of early volume contraction. All these will be magnified as protein deficiency worsens. The (possible) role played by prostaglandins, antidiuretic hormone, parathyroid hormone, and the reninaldosterone system in the hemodynamic changes and on the changes in urine concentration and salt and water handling will be studied. The interrelationships among substances such as urea, calcium, potassium and magnesium and the medullary generation of cyclic nucleotides and prostaglandins will be examined. Also, the effect of indomethacin, meclofenanate and angiotrnsin II inhibitors, on renal function will be studied ot assess the role of angiotensin II and prostaglandins in the consequences of low protein diet. Measurement of the status of glomerular receptors for this hormone will also be examined. These issues are of clinical importance since malnutrition is common in ambulatory and hospitalized patients and the morbidity of the state may be magnified by the subject's age. Because low protein diet may lead to diminish capacity to excrete a concentrated urine, dehydration may occur in the very young and old. In addition, hormonal inbalances may result from protein deficiency which may aggravate the conditions which accompany the malnourished state.